Breast or melanoma cells?

September 24 2008 post. As I think I have mentioned before, I subscribe to a million newsletters, among which is the Ralph Moss Report. This week Dr. Moss had a report on a shocking story written by Megan Scudellari and published in “The Scientist” on September 16th with the title “A case of mistaken identity. A cell line used in more than 650 published breast cancer studies may not be a breast cell line after all.“

 

In order to read the article, I had to sign up (for free) for “The Scientist” (http://www.the-scientist.com/). I then read the entire article. Ah no, “shocking” just doesn’t cover it.

 

The article begins as follows: Some breast cancer researchers may be studying the wrong type of cancer. A growing body of evidence suggests a cell line that’s been a cornerstone of metastatic breast cancer research over the last 25 years is in fact derived from melanoma cells. Say…whaaat?!

 

In 2000, a Georgetown University Ph.D. student, James Rae, wrote a paper on gene expression in 60 human cancer cell lines, including the purported breast cancer cell line, known as MDA-MB-435, which he placed with melanoma cell lines, not with breast cancer ones. It’s a long story…what follows are a few highlights.

 

In 2006, after extensive testing, Prof. Rae and a few colleagues determined once and for all that The true origin of MDA-MB-435 cells is a melanoma cell line called M14. This means (and I keep quoting from “The Scientist” report) that 25 years of breast cancer research on 435 may be based on an incorrect model system. […] Breast cancer hypotheses based on studies of the cell line may be incorrect, and treatments developed from it may ultimately be ineffective. I did a search in the PubMed database and found several studies questioning the continued use of this cell line in breast cancer research, such as this one: http://tinyurl.com/5y2qrc

 

The question arises: is this case unique? Apparently not. According to “The Scientist” report, Misidentification of cell lines is not rare; a short tandem repeat analysis of 100 human cell lines last year found 18 of the lines were incorrectly designated. But with 435, misidentification may be especially problematic. Because of the cell line’s unrivaled metastatic ability in mice, more than 650 studies using 435 as a breast cancer model have been published (including more than 60 so far this year). Despite growing doubts about its identity, with nothing to replace the model line, researchers have been unwilling to let it go. “There are people vested in using the cell line because they have grants involved,” said Rae.

 

Ah, money, money…hmmm, I guess it might be tough to choose between keeping your grant money or acknowledging the bitter fact that your research is probably based on a case of mistaken identity (=tongue-in-cheek)…but put yourselves in the shoes of a breast cancer patient currently in a clinical trial based on the Petri dish testing of this particular cell line. How would you feel?…Here is an approximation of how I would feel:

 

Well, there seems to be a “simple” solution to this problem, suggested by Prof. Rae himself, a breast cancer researcher: “The efforts spent over the years on studying MDA-MB-435 have not been wasted,” he wrote in the conclusion of his 2006 analysis of 435. “The many studies published using MDA-MB-435 as a model for breast cancer could now conceivably be reinterpreted as studies using M14 as a model for melanoma.” You can read the abstract of a study Prof. Rae et al wrote in 2007 here: http://tinyurl.com/48do7h Here it is clearly stated that this particular cell line can no longer be considered a model of breast cancer. But it can be used as a valuable new resource for the melanoma research community.

 

Aha! There you go! Administer breast cancer drugs (based on MDA-MB-435 testing) to melanoma patients…! I have a million questions but no time to search the Internet to find any answers right now. One of my questions: who is responsible for investigating such issues? What the… is the FDA doing about this? What about Congressional oversight? And why hasn’t this story been picked up by the popular press (I did a quick search, found zilch…)???!!!

 

I would like to end by quoting Dr. Moss: We are constantly being reminded that this is the era of evidence-based medicine. But if the very cell lines which have provided the foundation for breast cancer research for the past quarter century have now been conclusively shown to be melanoma cells, not breast cancer, how solid or trustworthy is the evidence on which current breast cancer treatment is based? Evidence built on such flawed foundations more closely resembles hearsay than science.

 

Whom can we trust???

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